Pharmacological Properties of T-type Ca2+ Current in Adult Rat Sensory Neurons: Effects of Anticonvulsant and Anesthetic Agents. Slobodan M. Todorovic and Christopher J. Lingle. Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110.
APStracts 4:267N, 1997.
ABSTRACT
We have used the whole cell patch-clamp method to study pharmacological properties of LVA Ca2+ current in freshly dissociated neurons from dorsal root ganglia of adult rats. Inward barium current (in the presence of internal fluoride to reduce L type HVA and external 1 m M w -conotoxin GVIA to block N type HVA current) was evoked from negative holding potentials of -90 mV to test potentials of -25 mV and showed complete inactivation during 200 ms test pulses. Amiloride blocked about 90% of current with half maximal block (EC50) of 75 m M and a Hill coefficient (n) of 0.99. LVA current was completely blocked by inorganic Ca2+ channel blockers: lanthanum (EC50 0.53 m M ) > zinc (EC50 =11.3 m M ) > cadmium (EC50 =20 m M ) > nickel (EC50=51 m M ) . The antiepileptics, ethosuximide (EC50=23.7 mM, n= 1.4), phenytoin (EC50 =7.3 m M , n=1.3), a -methyl-a -phenylsuccinimide (EC50 =170 m M , n=2.1) and valproic acid (EC50 = 330 m M , n=1.9) maximally blocked about 100%, 60%, 26% and 17% percent of T current, respectively. Another antiepileptic, carbamazepine (up to 100 m M ) and convulsants such as pentylenetetrazole (1 mM) and TBPS (50 m M ) had no effect on T current. Barbiturates completely blocked T current: thiopental (EC50= 153 m M , n= 1 . 2 ) > pentobarbital (EC50=334 mM ,n=1.2) > methohexital (EC50=502 m M, n=1.3) > phenobarbital (EC50=1.7 mM, n=1.2). Blockade by thiopental and pentobarbital did not show voltage- or use-dependence. General anesthetics blocked T current completely and reversibly: propofol (EC50=12.9 m M , n=1.3) > octanol (EC50=122 m M , n=1.2) > etomidate (EC50=205 m M , n=1.3) > isoflurane (EC50=303 m M , n=2.3) > halothane (EC50=655 m M , n=2.0) > ketamine (EC50=2.5 mM, n=1.1). Mibefradil, a novel Ca2+ channel blocker, blocked DRG T current in a voltage- and use-dependent fashion with an EC50 of 3 m M (n=1.3). When compared with results on other T currents, these data indicate that significant differences exist among different T currents in terms of pharmacological sensitivities. Furthermore, differences in pharmacological sensitivity of T currents among peripheral neurons, CNS, and neuroendocrine cells may contribute to the spectrum of effects of particular analgesic, anticonvulsant and anesthetic drugs. 

Received 21 July 1997; accepted in final form 19 September 1997.
APS Manuscript Number J602-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997